Protease(s) is/are associated with chromatin prepared from various tissues and Drosophila polytene chromosomes. However, nucleosomes prepared from different tissues contain very little protease activity. This suggests that the protease could be attached to structural framework of nuclei or metaphase chromosome. Preliminary experiments suggest that protease is tightly associated with nuclear matrix. We are presently studying in detail the association of protease with nuclear matrix and its role in the turnover of nuclear matrix proteins during the cell cycle of HeLa cells in culture. Inasmuch as nuclear matrix and chromosome scaffolds are intimately associated with nucleosomes the protease may play an important role in controlled turnover of nuclear proteins.